The spleen in the pathogenesis of ITP. (A) Autoantibodies bind to antigens on platelets, primarily gpIIb/IIIa, and gpIb/IX. (B) Splenic macrophages expressing FcγR internalize antibody-coated platelets, degrade them, and present platelet glycoprotein-derived peptides to autoreactive CD4⁺ T cells, which on activation interact with B cells through the CD40/CD40L interaction leading to somatic hypermutation and class switching. Autoreactive B cells differentiate into anti-platelet antibody-producing plasma cells that either stay in the spleen or migrate to the blood and bone marrow. (C) Megakaryocytes in the bone marrow express platelet glycoproteins such as gpIIb/IIIa and gpIb/IX, and autoantibodies against these antigens impair platelet production and contribute to megakaryocyte apoptosis. Circulating CD8 positive can also cause thrombocytopenia by direct cytotoxicity (not shown).